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Nervous System > Neurotransmitters, Receptors, etc... > Flashcards

Neurotransmitters, Receptors, etc... Flashcards

1
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2
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Mechanoreceptors

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•for sensing touch, pressure, vibration, proprioception, etc…

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3
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Chemoreceptors

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•for sensing chemicals including change in pH

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4
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Thermoreceptor

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•for sensing temperature

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5
Q

Nociceptor

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•for sensing pain •respond selectively to noxious stimuli •free nerve endings •do not adapt - continued stimulation results in continuous or repetitive firing of the nociceptor and in some cases, continued stimulation results in a decrease in the threshold at which the nociceptors respond (hypersensitivity) •pseudounipolar with cell bodies in the dorsal root ganglion •peripheral terminal with a terminal in the spinal cord or brainstem •when activated, pain neurotransmitters are released at both ends of the neuron

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6
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Photoreceptor

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•for sensing certain light wavelengths

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7
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Sensory receptors

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•collect information about the external and internal world •transducer stimuli into an electric graded potential (receptor potential) allowing it to encode the nature, location, intensity and duration of a stimulus •each receptor is more sensitive to certain types of stimulus called its adequate stimulus, than to others •use ionotropic or metabotropic mechanisms

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8
Q

Rapidly adapting receptors

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•response declines and may disappear entirely during a constant stimulus •act like miniature differentiators, producing a constant response to a steadily changing stimulus •hair follicles! •generate only two short bursts of spikes at the onset and offset of the stimulus - if the stimulus does not change, there are no spikes generated, therefore these receptors signal only a change in the stimulus

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9
Q

Slowly adapting receptors

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•start firing spikes (generating sequences of action potentials) at the onset of the stimulus and keep firing until the offset of the stimulus •even though the frequency of spikes may decrease to some degree from the onset to the offset of the stimulus - a phenomenon called spike frequency adaptation - these receptors never stop firing as long as the stimulus is acting on the receptor •the spikes or action potentials generated by these receptors register the nature of the stimulus, its onset, offset and duration •pain and stretch

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10
Q

Short receptors

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•less than a millimetre or so •don’t need to produce action potentials, they synapse on the peripheral processes of primary afferent neurons whose cell bodies lie in peripheral ganglia •taste, photoreceptors, mechanoreceptors of the inner ear

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11
Q

Pacinian corpuscules

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•encapsulated in a structure that looks like an onion with one nerve ending in the “core of the onion” •located deep in the skin (subdermal) all over the body, and have very large receptive fields •very rapidly adapting and convey vibration stimuli via alpha-beta fibers

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12
Q

Helical type ending wrapping around a hair follicle

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•aplha-beta nerve fibers that wrap around the endings of hair follicles and respond to brush and touch of the hair follicle •rapidly adapting with a small receptive field since they are found on individual hair follicles

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13
Q

Meissner corpuscules

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•encapsulated structures where the capsule is made of stacked Schwann cells •located most often in glamorous skin (hairless) near the surface •small receptive fields •rapidly adapting •convey mechanical stimuli via alpha beta nerve fibers •relay mechanical inputs related to changes in fine light touch and/or texture

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14
Q

Merkel disks

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•non encapsulated terminals located (like Meissner’s corpuscules) near the skin margin, but found in hairy and glabrous skin •small receptive fields •slowly adapting •covey mechanical “touch” stimuli by alpha beta nerve fibers •detecting edges, shapes and other fine details

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15
Q

Ruffini endings

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•encapsulated, located deep in the skin over the entire body including the internal organs •connected to the lattice of collagen in the skin and thus have large receptive fields •slowly adapting, convey stretch and sustained pressure vis alpha beta nerve fibers

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16
Q

Long receptors

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•generate action potentials as receptor potentials decay over short distances

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17
Q

Ionotropic

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•ligand gated ion channels within the cell membrane, activation causes a conformational change, leading to the immediate opening or closing of an ion channel •depolarisation or hyperpolarization •nicotinic cholinergic receptor: acetylcholine, NMJ, ANS (sympathetic and parasympathetic) •NMDA receptor: glutamate, allows Na+ and Ca++ ions into cell —> depolarisation, throughout CNS •GABA alpha receptors: GABA, allows Cl- into cell —-> hyperpolarization, CNS

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18
Q

Metabotropic

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•acts through a second messenger •cascade of biochemical events •G protein - ANS adregenic (sympathetic) muscarinic (parasympathetic), CNS •kinase - auto phosphorylation, insulin •nuclear- within cytoplasm, translocate to nucleus and bind to specific sequences on DNA —> gene transcription •slower than ionotropic •auto receptors - found on presynaptic neurons and auto regulate the release of NT

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19
Q

Somatosensory receptors

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•nerves of the somatosensory system receptors have peripheral process that originate in places like the skin, muscle, tendon, bone, tendons, joints or viscera •long axons, cell bodies in dorsal root ganglia (cranial nerve ganglia) and central processes that end in the CNS •some of the peripheral processes are free nerve endings (unspecialised afferent nerve fiber sending its signal to a sensory neuron), others have encapsulated endings and/or various types of accessory structures

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20
Q

Free nerve endings

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•unspecialised afferent nerve fiber sending its signal to a sensory neuron

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21
Q

Encapsulated accessory structures

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•nerve endings surrounded by stuff •barrier properties that can regulate the environment of receptive endings •transducer one form of energy into another, or a physical signal into a biological signal

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22
Q

Receptive fields

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•each receptor receives information from a restricted area of the body called a receptive field •not distributed uniformly, but are more densely packed in areas where fine acuity or control is needed •measured by two point discrimination

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23
Q

Two point discrimination

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•two fine tipped objects are placed on the surface close together and slowly separated until an individual can detect that there are two objects vs one •small receptive fields give rise to high acuity and large receptive fields give rise to ow acuity

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24
Q

Muscle spindles

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•receptor organs composed of small muscle fibers (intramural fibers) that detect muscle length, enclosed in a spindle shaped capsule •spindles are embedded in skeletal muscles and oriented so that they are stretched by anything that stretches the muscle •gamma motor neurons •regulates length of the central stretch sensitive portion of the intramural fiber and regulates its sensitivity to externally applied stretch •muscle spindles along with cutaneous receptors are important to proprioception •spindle fibers signal via type Ia (dynamic information) and Type II (static and dynamic) nerve fibers

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25
Q

Golgi tendon organs (GTOs)

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•detect muscle tension •networks of sensory endings interspersed among the collagen fibers of tendons •Ib nerve fibers •passive muscle stretch does not generate much tension, but contraction against a load does

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26
Q

Sensory fibers

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•grouped based on size/speed: Ia, Ib, alpha beta, alpha delta, C

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27
Q

Motor fibers

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•grouped based on size/speed: alpha, gamma

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28
Q

Topographic organisation

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•localisation in the brain

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29
Q

Raphe nuclei

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•can be found along the midline in the brainstem from the midbrain to the medulla •synthesis of serotonin •raphe nuclei —-> along medial forebrain bundle through hypothalamus —-> widespread regions over the entire cerebral cortex and also to the cerebellum and down the lateral funiculus of the spinal cord •continually secrete neurotransmitter establishing a resting state that varies over different levels of consciousness

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30
Q

Serotonin

A

•synthesised in raphe nuclei in brainstem •acts on postsynaptic receptors to produce a number of effects •GPCRs labelled as 5-HT receptors with the exception of 5-HT3 (cationic channel) •actions determined by reuptake through a transporter as well as by metabolism by monoamine oxidase (MAO) •decreased levels linked to depression, OCD, Tourette’s, panic attacks and eating disorders •synthesised from tryptophan by tryptophan hydroxylase and L-aromatic acid amino acid decarboxylase

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31
Q

SSRIs

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•selective serotonin reuptake inhibitors •block the reuptake of serotonin from the synaptic cleft

32
Q

Norepinephrine

A

•synthesised in neurons throughout most parts of the brainstem - rostrum pons “locus ceruleus” (project via medial forebrain bundle to the cerebral cortex and also to cerebellum), medullary reticular formation (spinal cord), dorsal motor nucleus in the medulla, and the nucleus of the solitary tract •neurons that make NE (noradrenergic) are located more laterally, away from the midline as compared to serotonergic neurons •acts at 5 different GPCRs - alpha 1, alpha 2, beta 1, beta 2, beta 3 •low levels linked to depression •reuptake by monoamine oxidase (MAO) and COMT metabolism •synthesised from tyrosine by tyrosine hydroxylase —-> DOPA by DOPA decarboxylase —> NE by dopamine beta-hydroxylase

33
Q

Dopamine

A

•unlike serotonin and NE, dopaminergic neurons do not bathe the entire brain but they do project via the medial forebrain bundle to several structures including the temporal cortex, limbic lobe, frontal and prefrontal cortex as well as to the basal ganglia •GPCRs D1-5 - D1 and D5 coupled to G alpha s and D2, D3, D4 coupled to G alpha i •many of the neurons involved in psychiatric disorders project from the ventral tegmental area of the midbrain •schizophrenia •synthesised from tyrosine by tyrosine hydroxylase —-> DOPA by DOPA decarboxylase

34
Q

Acetylcholine

A

•bathes the CNS, secreted from reticular formation of the brainstem and the basal nucleus •nicotinic ion channels •muscarinic receptors - GPCR M1-M5 all couple to G alpha q •decreased levels lead to dementia, may play a role in autism, REM sleep cycle •acetylcholinesterase lies in the synapse and degrades acetylcholine •synthesised in the cholinergic nerve terminals by the enzyme choline acetyltransferase using acetyl coenzyme A and choline

35
Q

MAOi, TCAs, SNRIs

A

•monoamine oxidase inhibitors •tricyclic antidepressants •serotonin and norepinephrine reuptake inhibitors •medications that raise the levels of both serotonin and norepinephrine

36
Q

Noxious

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•damaging stimuli

37
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Transduction

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•first step of noxious signal processing •process by which noxious stimuli are converted to electrical signals by nociceptors

38
Q

Axon reflex

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•peripheral release of pain neurotransmitters leading to peripheral changes that are recognised indicators of pain - redness, swelling, tenderness

39
Q

Hyperalgesia

A

•when nociceptors become sensitised, they respond to noxious stimuli more vigorously - same stimulus now produces more pain

40
Q

Allodynia

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•when a non noxious stimulus causes pain

41
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Transmission

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•second step of noxious signal processing •information from the periphery is relayed to the brainstem or spinal cord —> thalamus —> cortex •noxious information is relayed mainly via two different types of primary afferent nociceptive neurons that conduct at different velocities - C fibers and alpha delta fibers

42
Q

C Fibers

A

•non-myelinated fibers •0.5-2 m/sec •mechanical, thermal, chemical - aka “polymodal C nociceptors” •dull, diffuse, poorly localised pain that follows initial pain - “second pain” •enter medially into dorsal root entry zone compared to larger touch fibers

43
Q

Alpha delta Fibers

A

•thinly myelinated •conduct 2-20m/sec •mechanical and thermal •initial, sharp, well localised pain that immediately follows a noxious stimulus - “first pain” •enter medially into dorsal root entry zone compared to larger touch fibers —> Lissauer’s tract, travel rostral or caudal for up to 4 spinal cord segments before entering dorsal horn of spinal cord —-> second order neuron (can become sensitised - central sensitisation”)in the superficial layer of the spinal cord, laminate I and II —> second order neurons send axons across the midline into the anterolateral aspect of the S.C. white mattter to join many other similar fibers —-> STT —> thalamus, 3rd order neurons —-> somatosensory cortex

44
Q

Glutamate

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•one of the most important neurotransmitters for pain •can interact with both ion channels and second messenger receptors

45
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Substance P

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•neurotransmitter associated with the transmission of pain •peptide

46
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Modulation

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•third step of noxious signal processing •represents changes that occur in the nervous system in response to noxious stimuli •inhibition of noxious pain signals received at the dorsal horn of the SC so that transmission to higher centers is modified •endorphins and enkephalins - endogenous peptides that produce pain relief

47
Q

Supraspinal descending modulatory systems

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•fourth step in noxious signal transmission •activated by endorphins/enkephalins •periaqueductal grey region of the midbrain —> sites in the medullary RF and locus ceruleus •disinhibition - inhibition of a tonically active GABAergic inhibitory neuron that innervates the descending neurons •dorsolateral funiculus —>synapse with incoming primary afferents, second order neurons and/or interneurons that may release endorphins/enkephalins •descending pain modulatory neurons release NT in the spinal cord, serotonin (5HT) and NE - these two directly inhibit the release of pain NT from the incoming nociceptive afferent signal and inhibit second order transmission - and or activate small opioid containing interneurons in the spinal dorsal horn to release endorphins/enkephalins

48
Q

Sites of opioid action

A

•activating the opioid receptors in the brainstem and turning “on” the descending systems (through disinhibition) •activating opioid receptors on the second order pain transmission cells of the SC and brainstem to prevent the ascending transmission of the pain signal •activating opioid receptors on the primary nociceptive pain fibers on both the central and peripheral terminals to inhibit transduction of the pain signal

49
Q

Sensory component

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•pain perception is the final part of the noxious signal transmission process where there is subjective interpretation of the cortex of the stimulus as pain •stimulus classified as noxious, intensity decoded, location identified

50
Q

Affective component

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•pain perception is the final part of the noxious signal transmission process where there is subjective interpretation of the cortex of the stimulus as pain •before sensory component, the cortex relates the situation and history of the noxious stimulus

51
Q

Synaptic plasticity

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•changes in processes of transmission and/or transduction -presynaptic increases or decreases in transmitter release -postsynpatic increases or decreases in response to transmitter •peripheral or central sensitisation •seconds to minutes, may be reversible

52
Q

Cellular plasticity

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•changes in cell phenotype -existing proteins being up or down regulated -expression of proteins that were previously NOT expressed by that cell -changes in subunit composition of channels -remodelling of membranes due to changes in protein trafficking and/or membrane insertion •hours to days, may be reversible

53
Q

Systems plasticity

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•months to years, not reversible •abnormal, neuropathic pain •chemotherapy, diabetic neuropathy

54
Q

Synapse

A

•the junction between two neurons •electrical and chemical

55
Q

Synaptic transmission

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•how information is transferred from the presynaptic to the postsynaptic neuron

56
Q

Electrical synapses

A

•involve direct continuity between adjacent cells at the point of contact via gap junctions •electrical currents, generated by the activity of channels in the presynaptic cell are conducted to the postsynaptic cell by means of a direct flow of ions through the gap junction •the gap junction is a dodecameric complex of proteins called connexins which combine to form an aqueous pore that bridges the cytoplasmic compartments of the two cells •electrical synapses allow for rapid and synchronous firing of interconnected cells •can flow unidirectionally or bidirectionally and is typically excitatory •important in coordinating electrical activity of glial cells, Schwann cells, cardiac cells and some smooth muscle cells •minor role in mammalian central nervous system

57
Q

Chemical synapses

A

•predominant class of synapses in the mammalian CNS •more complex than electrical, offer more versatility than electrical, involved in behaviours that are more complex •separated by a small space called the synaptic cleft •can mediate an inhibitory or excitatory action •can modulate or amplify other neuronal signal •point of functional communication between two neurons or between a neuron and a target cell •proximity of a synapse to a trigger zone (axon hillock) is important in determining its effectiveness

58
Q

Varicosities

A

•unique synapses (chemical) along an axon

59
Q

Bouton

A

•synapse (chemical) at the end of an axon

60
Q

Glutamate and aspartate

A

•typically the major excitatory neurotransmitters

61
Q

Gamma-aminobutyric acid (GABA) and glycine

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•typically the major inhibitory neurotransmitters

62
Q

Acetylcholine, and biogenic amines - dopamine, norepinephrine, serotonin

A

•small molecule neurotransmitters

63
Q

Peptide neurotransmitters

A

•one of the four classes of neurotransmitters •enkephalins, endorphins etc.. •synthesised from the nucleus through the common transcription and translation processes and imported into vesicles as the y pass through the Golgi apparatus

64
Q

Axodendritic

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•axon (synapse) to dendrite •often excitatory

65
Q

Axosomatic

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•axon (synapse) to soma •often inhibitory

66
Q

Axoaxonic

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•axon (synapse) to axon •excitatory/inhibitory

67
Q

5 steps of chemical synaptic transmission

A
  1. Synthesis of neurotransmitter within the presynaptic neuron 2. Storage of the neurotransmitter within synaptic vesicles in the presynaptic nerve terminal 3. Release upon depolarisation, and diffusion across the synaptic cleft 4. Interaction of the neurotransmitter with specific receptors located on the membrane of the postsynaptic cell 5. Termination of the synaptic actions of the neurotransmitter
68
Q

GABA

A

•synthesised from glutamate by glutamic acid decarboxylase

69
Q

Storage of neurotransmitters

A

•NT stored in the presynaptic nerve terminal travel both anterograde and retrograde via the microtubule and special protein carriers •often small molecule NTs are resynthesized in the cytoplasm of the of the presynaptic nerve terminal or between the vesicles •small NT molecules can be transported into the synaptic vesicle by specific transporter transporter proteins located in the membrane of the synaptic vesicle [reserpine prevents the transport of catelcholamines and indolamines into synaptic vesicles —> lowers levels of dopamine, NE and serotonin] •storage in the vesicles protects NTs from degradation, provides a mechanism of transport to the neuronal end and enable the NT to be released upon depolarisation •presynaptic vesicles also contain proteins that 1) sense the concentration of Ca++ 2) hold the vesicle for release 3) proteins that are involved in the docking, release and uptake of the vesicle within the presynaptic nerve terminal [often a target for several toxins, including tetanus toxin and botulinum toxin - inhibit release of NTs] [alpha-latrotoxin stimulates the release of NTs - from black widow spiders]

70
Q

Release of neurotransmitters

A

•voltage dependent Na+ and K+ channels are present in the axon and mediate the fluxes required for action potential propagation - NOT PRESENT in presynaptic terminals •VGCC are in the presynaptic terminal, depolarisation causes Ca++ to flow down their electrochemical gradient into the presynaptic terminal —> Ca++ binds to synaptic vesicles, which then fuse with the membrane of the presynaptic terminal —-> exocytosis release of NT into synaptic cleft •NT diffuses acros the synaptic cleft to reach receptors located on the postsynaptic target neuron

71
Q

Quantum

A

•the complement of NT molecules within a single synaptic vesicle

72
Q

Quantal release

A

•fusion of individual vesicles with the presynaptic nerve terminal membrane results in a release of NT

73
Q

Termination of synaptic actions of neurotransmitters

A

1)endocytosis - vesicular reuptake [amitriptyline, imiprine, desipramine] [SSRI - fluoxetine, paroxetine, sertaline] [cocaine] •glutamate, aspartate, GABA, glycine, NE, dopamine, serotonin •Cathrin - marks the vesicle for endocytosis •dynamic - GTPase calcium dependent protein necessary for pinching off the vesicle from the presynaptic membrane) 2) diffusion •dilution •all NTs 3)metabolism •acetylcholine - acetylcholinesterase (at NMJ - postsynaptic, at CNS - presynaptic) [nerve gas, SARIN, DIAZINON (pesticide)] •dopamine and NE - monoamine oxidase (MAO) [phenelzine, selegine]and catechism-O-methyltransferase (COMT) -Final metabolite of dopamine = homovanillic acid (HVA) •serotonin - monoamine oxidase —> hydroxyindole acetic acid (5-HIAA) •peptides - exopeptidases or endopeptidases in the synaptic cleft -final metabolite of NE = 3-methods-4hydroxyphenylglycol (MHPG)

74
Q

Electro physiological sequelae of NT receptor activation

A

•excitatory post synaptic potential (EPSP) -depolarisation of the postsynaptic cell membrane -graded potential •inhibitory post synaptic potential (IPSP) -hyperpolarization •graded potential •individual EPSPs or IPSPs produce only small perturbations of the post synaptic cell membrane potential -if the cell is to be excited to threshold, it generally requires EPSP input from any different cells and/or repeated excitatory input from a few cells •convergence and integration •axon hillock has a high number of VGSC, key site for integration (summation) -temporal summation -spatial summation

75
Q

Synaptic disinhibition

A

•double inhibition

Nervous System (11 decks)

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